Descargar (PDF, Unknown)

VELOCITY
A Prospective, Randomized Trial of
Peritoneal Hypothermia in Patients with
Acute STEMI Undergoing PCI
Gregg W. Stone, MD
Columbia University Medical Center
The Cardiovascular Research Foundation
On behalf of Graham Nichol, Warren Strickland, David Shavelle,
Akiko Maehara, Ori Ben-Yehuda, Philippe Genereux, Ovidiu Dressler,
Rupa Parvataneni, Melissa Nichols, John McPherson, Gérald Barbeau,
Abhay Laddu, Jo Ann Elrod, Griffeth W. Tully, and Russell Ivanhoe
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
• Consultant
Company
• Velomedix
All faculty disclosures are available on the CRF Events App and online at www.crf.org/tct
Background
• Systemic hypothermia (≤34.9°C) may reduce
infarct size if established before reperfusion
• Peritoneal lavage has a well-established
safety profile for diagnosis of blunt
abdominal injury in patients with trauma,
and for treatment of accidental hypothermia,
end-stage renal disease, and cancer
• The large surface area of the bowel may
facilitate rapid hypothermia, safely reducing
infarct size
Objective
• We therefore sought to assess the
feasibility, safety and efficacy of
systemic hypothermia induced by
peritoneal lavage in patients with
STEMI prior to primary PCI
Velocity Trial Design
Symptoms of STEMI between 30 minutes and 6 hours
ST-segment elevation ≥2 mm in ≥2 continuous ECG leads
Intended for primary PCI
Maximum 60 patients
Randomize 1:1
Cardiac
catheterization/PCI
Peritoneal hypothermia
followed by cardiac
catheterization/PCI
Cardiac MRI at 3-5 days and at 30 (±7) days
Clinical follow-up at 30 days and 6 months
Key Exclusion Criteria
• Contraindications to peritoneal lavage (e.g. prior intraperitoneal surgery,
profound obesity, abdominal aortic aneurysm, or massive ascites)
• Temperature-sensitive hematological dyscrasias or vasospastic disorders
• Cardiac arrest, pulmonary edema or cardiogenic shock
• Oxygen-dependent COPD
• Prior MI
• Active bleeding, thrombolytic therapy or chronic oral anticoagulant use
• Known hemoglobin <9 mg/dL, platelet count <100,000 or >750,000
cells/mm3, serum creatinine >2.0 mg/dL, dialysis or abnl liver function
• Allergy or intolerance to contrast or study drugs
• Contraindications for MRI
• Pregnant or nursing
• Comorbidities with life expectancy <1 year
• Inability to provide informed written consent
Velomedix Automated Peritoneal Lavage
System
Touchscreen
interface
Controller console
Peritoneal
catheter
Solid state
cooling,
warming
Refrigerator
(disposable fluid
bags inside)
Lavage
fluid line
Esophageal core
temperature
probe
Shivering prophylaxis and treatment
Pre-PCI: Buspirone; meperidine, forced-air warming
blanket
If needed: Fentanyl, magnesium, dexmedetomidine
 Hypothermia to 34.9°C is induced
before PCI by lavaging the peritoneal
cavity with temperature-controlled 2.5 4.5 liters of lactated Ringer’s solution
 Further cooling occurs to a target
temperature of 32.5°C, which is
maintained for 3 hours post-PCI, after
which the system initiates active rewarming and then fluid drainage
Endpoints
• Device success (hypothermia): Core temperature ≤34.9°C
before PCI
• Primary safety endpoint: Composite rate of death,
reinfarction, ischemia-driven TVR, major bleeding, sepsis,
pneumonia, peritonitis, severe arrhythmias, or renal failure
occurring within 30 (±7) days
• Primary efficacy endpoint: Infarct size assessed by cardiac
MRI on day 3-5 (%LV mass)
• Other endpoints:
• MRI: MVO at 3-5 days, and LV volumes and EF at 3-5 and 30 days
• TIMI flow, ST-segment resolution
• Clinical: MACE (cardiac death, reinfarction, or ischemia-driven TVR);
ARC stent thrombosis
VELOCITY Trial Organization
Principal investigator: Gregg W. Stone, Columbia University Medical
Center, New York, NY
Co-principal investigator: Graham Nichol, University of WashingtonHarborview Center for Prehospital Emergency Care, Seattle, WA
Sponsor, site management and data monitoring: Velomedix, Inc.,
Menlo Park, CA; Russell Ivanhoe, Griffeth W. Tully
Data management and analysis: The Cardiovascular Research
Foundation (CRF), New York, NY; Ori Ben-Yehuda, Melissa Nichols,
Ovidiu Dressler, Rupa Parvataneni
Coronary angiographic core laboratory: CRF; Philippe Genereux
Cardiac MRI core laboratory: CRF; Steven D. Wolff, Akiko Maehara
ECG core laboratory: St. Louis University, St. Louis, MO; Bernard
Chaitman, Abhay Laddu
Clinical events committee, and data safety and monitoring board:
David Beiser, Joseph P Carrozza Jr., Sam Tisherman, Kyle D. Rudser
VELOCITY Trial Participating Hospitals
and Principal Investigators
Huntsville Hospital, Huntsville, AL; Warren Strickland
USC/Los Angeles County Hospital, Los Angeles, CA; David Shavelle
Vanderbilt Medical Center, Nashville, TN; John McPherson
Hospital Laval, Laval, Quebec City, Canada; Gérald Barbeau
Northeast Georgia Heart Center Gainesville, GA; Allison Dupont
Ochsner Medical Center, New Orleans, LA; Steve Jenkins
Royal Jubilee Hospital, Victoria, BC, Canada; Eric Fretz
Patient Flow
Symptoms of STEMI between 30 minutes and 6 hours
ST-segment elevation ≥2 mm in ≥2 continuous ECG leads
Intended for primary PCI
N=54 at 7 US and Canadian centers
Randomize 1:1
Cardiac
catheterization
N=26
PCI
performed
N=25
No target
lesion
N=1
Peritoneal hypothermia
followed by cardiac
catheterization
N=28
Peritoneal access
successful/attempted
N=26/27 (96.3%)
Hypothermia established
N=26
PCI performed
N=27
No peritoneal
access;
No PCI.
Surgery for
aortic dissection
N=1
Baseline Features
Control
(n=26)
Hypothermia
(n=28)
P value
Age in years
57.5 [52, 63]
57 [47, 65]
0.51
Male gender
21 (80.8%)
25 (89.3%)
0.46
Hypertension
9 (34.6%)
14 (50.0%)
0.25
Hyperlipidemia
6 (23.1%)
10 (35.7%)
0.31
Diabetes
6 (23.1%)
6 (21.4%)
0.88
11/25 (44.0%)
12 (42.9%)
0.93
0
0
-
12 (46.2%)
13 (46.4%)
0.98
Medical history
Current smoking
Prior MI
Anterior infarct (ECG)
Baseline and Procedural Medications
Control
(n=26)
Hypothermia
(n=28)
P value
Aspirin
19 (73.1%)
23 (82.1%)
0.42
ADP antagonist
8 (30.8%)
5 (17.9%)
0.27
Beta blocker
4 (15.4%)
7 (25.0%)
0.38
0
0
-
1 (3.8%)
0
0.48
Medications on admission
ACEI/ARB
Statin
Medications prior to and/or during PCI
Heparin
16 (61.5%)
14 (50.0%)
0.39
Bivalirudin
21 (80.8%)
21 (75.0%)
0.61
Aspirin
18 (69.2%)
22 (78.6%)
0.43
ADP antagonist, any
20 (76.9%)
20 (71.4%)
0.65
Clopidogrel
9 (34.6%)
11 (39.3%)
0.72
Prasugrel
10 (38.5%)
3 (10.7%)
0.02
Ticagrelor
2 (7.7%)
6 (21.4%)
0.25
10 (38.5%)
13 (46.4%)
0.55
GP IIb/IIIa inhibitor
Angiographic Outcomes (core lab)
Control
Hypothermia
n=25
n=26
LAD
10 (40.0%)
11/25 (44.0%)
0.77
LCX
2 (8.0%)
3/25 (12.0%)
>0.99
RCA
12 (48.0%)
11/25 (44.0%)
0.78
SVG
1 (4.0%)
0/25 (0%)
>0.99
0/1
18 (72.0%)
21 (80.8%)
0.46
2
6 (24.0%)
1 (3.8%)
0.05
3
1 (4.0%)
4 (15.4%)
0.35
n=24
n=26
0 (0%)
0 (0%)
-
2
2 (8.3%)
5 (19.2%)
0.42
3
22 (91.7%)
21 (80.8%)
0.42
28 [20, 36]
26 [23, 34]
0.77
Angiography, baseline
P value
Target vessel
TIMI flow
Angiography, post-PCI
TIMI flow
0/1
TIMI frame count
Electrocardiography (core lab)
Control
Hypothermia
P value
N=26
N=28
Summed
9.1 [6.5, 12.1]
7.8 [6.0, 11.7]
0.48
Maximum lead
2.3 [2.1, 3.6]
2.9 [2.0, 3.5]
0.87
ST-segment resolution
N=26
N=26
Complete (≥70%)1
5 (19.2%)
5 (19.2%)
>0.99
Complete (≥70%)2
7 (26.9%)
7 (26.9%)
>0.99
Baseline
ST-segment elevation, mm
60 mins post-PCI
1From
summed leads; 2From maximum lead
MRI Results at Day 3-5
Control (n=20)
Hypothermia (n=26)
P value
4 (3, 4)
4 (3, 5)
0.53
125.5 (109.5, 135,5)
123 (107, 142)
0.80
Area at risk (grams)
35.1 (20.4, 50.5)
34.2 (26, 51.6)
0.56
Area at risk (% LV mass)
26.8 (16.7, 40.6)
26.1 (22.7, 34.4)
0.69
Infarct mass (grams)
20.8 (10.9, 27.6)
22.2 (15.6, 30.1)
0.44
Infarct mass/area at risk (%)
55.8 (43.8, 67.2)
67.3 (48.9, 73.3)
0.36
Myocardial salvage (%)
44.2 (32.8, 56.2)
32.7 (26.7, 51.1)
0.36
Primary efficacy endpoint:
Infarct size (% total LV mass)
16.1 (10.0, 22.2)
17.2 (15.1, 20.6)
0.54
MVO (grams)
0 (0, 0.2)
0 (0, 0.7)
0.57
MVO (% total LV mass)
0 (0, 0.2)
0 (0, 0.5)
0.64
LV end-diastolic volume (mL)
161 (137.5, 172)
159 (125, 191)
0.80
LV end-systolic volume (mL)
83.3 (66.8, 102)
81.9 (71, 119)
0.63
LV stroke volume (mL)
75.2 (61.4, 81.5)
75.4 (61.1, 84)
0.78
LV ejection fraction (%)
46.3 (42.6, 50.6)
43.3 (37.4, 52)
0.37
8 (4, 11.5)
8 (6, 10)
0.52
Time from PCI (days)
LV myocardial mass (grams)
Abnormal wall motion score
Subgroup Analysis for Infarct Size at Day 3-5
Infarct Size (%LV mass)
35
30
Control
Hypothermia
P=0.39
P=0.68
25
P=0.17
P=0.11
20
15
10
5
0
LAD
(N=20)
Non-LAD
(N=23)
Infarct vessel
Pinteraction = 0.35
≤3 hours
(N=34)
>3 hours
(N=10)
Symptom onset to hospital arrival
Pinteraction = 0.25
Clinical Events at 30 Days
25
Control (n=26)
Hypothermia (n=28)
21.4
Event rate (%)
20
P=0.02
P=0.24
15
P=0.24
10.7
10.7
10
5
0
0.0
Primary safety
composite endpoint
0.0
MACE
0.0
Stent thrombosis
Major Adverse Cardiac Events
Control (n=26)
Hypothermia (n=28)
P value
Composite MACE
0
3 (10.7%)
0.24
Cardiac death
0
1 (3.6%)*
>0.99
Reinfarction
0
1 (3.6%)**
>0.99
Ischemia-driven TVR
0
3 (10.7%)**
0.24
Stent thrombosis
0
3 (10.7%)
0.24
Acute (≤24 hrs)
0
2 (7.1%)
0.49
Subacute (1-30d)
0
1 (3.6%)
>0.99
Definite
0
3 (10.7%)
0.24
Probable
0
0
-
30-day events
*Pt with aortic dissection mimicking STEMI died after surgery (no PCI or hypothermia);
**Due to stent thrombosis
Limitations
• Modest sample size, not powered for
efficacy
• Unblinded
• Non-anterior as well as anterior infarcts
• Level of optimal cooling prior to PCI is
unknown
• Long-term follow-up is not available
Conclusions
• Controlled systemic hypothermia through
automated peritoneal lavage may be rapidly
established in pts with evolving STEMI
undergoing primary PCI at the expense of a
modest increase in door-to-balloon time
• In the present randomized trial, peritoneal
hypothermia was associated with an
increased rate of adverse events (including
stent thrombosis) without reducing infarct
size